Intraventricular Infusion of the Neurotrophic Protein S100B Improves Cognitive Recovery after Fluid Percussion Injury in the Rat

Abstract

Elevated serum S100B levels have been shown to be a predictor of poor outcome after traumatic brain injury (TBI). Experimental data, on the other hand, demonstrate a neuroprotective and neurotrophic effect of this calcium-binding protein. The purpose of this study was to examine the role of increased S100B levels on functional outcome after TBI. Following lateral fluid percussion or sham injury in male Sprague Dawley rats (n = 56), we infused S100B (50 ng/h) or vehicle into the cerebrospinal fluid of the ipsilateral ventricle for 7 days using an osmotic mini-pump. Assessment of cognitive performance by the Morris water maze on days 30-34 after injury revealed an improved performance of injured animals after S100B infusion (p < 0.05), when compared to vehicle infusion. Blood samples for analysis of clinical markers of brain damage, S100B and neuron specific enolase, taken at 30 min, 3 h, 4 h, 2 days, or 5 days showed a typical peak 3 h after injury (p < 0.01), and higher serum levels correlated significantly with an impaired cognitive recovery (p < 0.01). The correlation of higher serum S100B levels with poor water maze performance may result from injury induced opening of the blood-brain barrier, allowing the passage of S100B into serum. Thus while higher serum levels of S100B seem to reflect the degree of blood-brain barrier opening and severity of injury, a beneficial effect of intraventricular S100B administration on long-term functional recovery after TBI has been demonstrated for the first time. The exact mechanism by which S100B exerts its neuroprotective or neurotrophic influence remains unknown and needs to be elucidated by further investigation.

S100 and Impact of ECT on Depression and Cognition

“…Neuroprotective effects of low concentrations of S100-beta are described in animal studies, resulting in improved learning and cognitive functioning through effects on neural plasticity and glial proliferation. 9,12,56 In parallel with these findings is the observation that ECT can give rise to sprouting and cell proliferation, particularly in serotonergic neurons in the hippocampal region. 57,58 Interestingly, higher baseline S100-beta concentrations in the neuroprotective range have been associated with better treatment response 50 and better cognitive functioning 59 in depressed patients.…”

S100B Serum Levels and Word Memory Processing in Remitted Major Depression as Reflected by Brain Potentials

“…Animal experiments have demonstrated that intracerebral injection or infusion of S100 could improve cognitive recovery after traumatic brain injury [29] , facilitate memory processing in a dose-dependent way [30] and lead to the consolidation of passive avoidance memory [31] . Recently, histopathological studies demonstrated that mood disorders were characterized by disease-specific glial pathology [32,33] .…”

S100B Inhibition Reduces Behavioral and Pathologic Changes in Experimental Traumatic Brain Injury

“…14,15 Multiple experimental TBI models have shown significant increases in S100B levels in the brain early after TBI 28 and persisting up to 5 days. 29,30 Intraventricular infusion of S100B resulted in a significant improvement in memory function after lateral fluid percussion-induced brain injury, 29 but higher serum levels of S100B were correlated with impaired cognitive performance. The latter finding is in agreement with many clinical observations and was thought to reflect activation of secondary injury mechanisms.…”